Difference between revisions of "Armstrong 2003 J Biol Chem"
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|abstract=The mitochondrial permeability transition ( | |abstract=The mitochondrial permeability transition (mtPT) is a key event in apoptotic and necrotic cell death and is controlled by the cellular redox state. To further investigate the mechanism(s) involved in regulation of the mtPT, we used diethylmaleate to deplete GSH in HL60 cells and increase mitochondrial reactive oxygen species (ROS) production. The site of mitochondrial ROS production was determined to be mitochondrial respiratory Complex III (cytochrome ''bc''<sub>1</sub>), because (''1'') stigmatellin, a Q<sub>o</sub> site inhibitor, blocked ROS production and prevented the mtPT and cell death and (''2'') cytochrome ''bc''<sub>1</sub> activity was abolished in cells protected from the redox-dependent mtPT by stigmatellin. We next investigated the effect of pretreating cells with coenzyme Q<sub>10</sub> analogs decylubiquinone (dUb) and ubiquinone 0 (Ub0) on the redox-dependent mtPT. Pretreatment of HL60 cells with dUb blocked ROS production induced by GSH depletion and prevented activation of the mtPT and cell death, whereas Ub0 did not. Since we also found that dUb did not inhibit cytochrome ''bc''<sub>1</sub> activity, the mechanism of protection against redox-dependent mtPT by dUb may depend on its ability to scavenge ROS generated by cytochrome bc1. These results indicate that dUb, like the clinically used ubiquinone analog idebenone, may serve as a candidate antioxidant compound for the development of pharmacological agents to treat diseases where there is an oxidative stress component. | ||
|editor=Komlodi T | |editor=Komlodi T | ||
}} | }} | ||
Latest revision as of 16:59, 11 March 2021
| Armstrong JS, Whiteman M, Rose P, Jones DP (2003) The Coenzyme Q10 analog decylubiquinone inhibits the redox-activated mitochondrial permeability transition: role of mitcohondrial [correction mitochondrial] complex III. J Biol Chem 278:49079-84. |
Armstrong JS, Whiteman M, Rose P, Jones DP (2003) J Biol Chem
Abstract: The mitochondrial permeability transition (mtPT) is a key event in apoptotic and necrotic cell death and is controlled by the cellular redox state. To further investigate the mechanism(s) involved in regulation of the mtPT, we used diethylmaleate to deplete GSH in HL60 cells and increase mitochondrial reactive oxygen species (ROS) production. The site of mitochondrial ROS production was determined to be mitochondrial respiratory Complex III (cytochrome bc1), because (1) stigmatellin, a Qo site inhibitor, blocked ROS production and prevented the mtPT and cell death and (2) cytochrome bc1 activity was abolished in cells protected from the redox-dependent mtPT by stigmatellin. We next investigated the effect of pretreating cells with coenzyme Q10 analogs decylubiquinone (dUb) and ubiquinone 0 (Ub0) on the redox-dependent mtPT. Pretreatment of HL60 cells with dUb blocked ROS production induced by GSH depletion and prevented activation of the mtPT and cell death, whereas Ub0 did not. Since we also found that dUb did not inhibit cytochrome bc1 activity, the mechanism of protection against redox-dependent mtPT by dUb may depend on its ability to scavenge ROS generated by cytochrome bc1. These results indicate that dUb, like the clinically used ubiquinone analog idebenone, may serve as a candidate antioxidant compound for the development of pharmacological agents to treat diseases where there is an oxidative stress component.
• Bioblast editor: Komlodi T
